[Recent advances in antiviral drugs--antiviral agents to HCMV, HHV-6, and HHV-7].
Foscarnet, Phosphonoformate, has recently approved for the treatment of HCMV retinitis in AIDS patients in Japan. It inhibits the viral DNA polymerase and effective against ganciclovir-resistant HCMV. Cidofovir, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine, a new acyclic nucleotide phosphonate analogues has potent activity against HCMV retinitis in AIDS at 3-7.5 mg/kg/week, once/week with concomitant oral probenecid and saline prehydration to prevent nephrotoxicity. The highest potency and selectivity against HHV-6 and HHV-7 was demonstrated S2242 (N7-isomer of 6-deoxy-ganciclovir). Ganciclovir, foscarnet, and cidofovir also exhibited selective inhibitory activity to these viruses, although the activities were not so remarkable compared with in case of HCMV. Thymidine kinase-dependent drugs (acyclovir, brivudin) showed little, if any, activity. These results suggest a structural homology of the DNA polymerase and a lack of TK gene among these three beta-herpesviruses.
Takahashi
K
K
Department of Microbiology, Fukushima Medical College.
D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology*; D015774:Ganciclovir / Q000494:pharmacology*; D006566:Herpesviridae Infections / Q000188:drug therapy; D015654:Herpesvirus 6, Human / Q000187:drug effects*; D016199:Herpesvirus 7, Human / Q000187:drug effects*; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011687:Purines; C092709:S 2242; D017245:Foscarnet; D003596:Cytosine; D013937:Thymidine Kinase; D000077404:Cidofovir; D015774:Ganciclovir